Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue

Overview

Journal Sci Rep

Specialty Science

Date 2017 Apr 4

PMID 28368043

Citations 34

Authors

Takeichiro Nakane

Hidetoshi Masumoto

Joseph P Tinney

Fangping Yuan

William J Kowalski

Fei Ye

Amanda J LeBlanc

Ryuzo Sakata

Jun K Yamashita

Bradley B Keller

Affiliations

Soon will be listed here.

Abstract

The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days. ME-ECTs displayed the lowest dead cell ratio (p < 0.001) and matured into 0.5 mm diameter myofiber bundles with greater 3D cell alignment and higher active stress than PS-ECTs. Increased initial ECT cell number beyond 6 M per construct resulted in reduced cell survival and lower active stress. The 6M-ME-ECTs implanted onto 1 week post-infarct immune tolerant rat hearts engrafted, displayed evidence for host vascular coupling, and recovered myocardial structure and function with reduced scar area. We generated a larger (30 × 30 mm) ME-ECT to confirm scalability. Thus, large-format ECTs generated from hiPSC-derived cardiac cells may be feasible for large animal preclinical cardiac regeneration paradigms.

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References

Schaaf S, Shibamiya A, Mewe M, Eder A, Stohr A, Hirt M . Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology. PLoS One. 2011; 6(10):e26397. PMC: 3197640. DOI: 10.1371/journal.pone.0026397. View

Christoforou N, Liau B, Chakraborty S, Chellapan M, Bursac N, Leong K . Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues. PLoS One. 2013; 8(6):e65963. PMC: 3681781. DOI: 10.1371/journal.pone.0065963. View

Bauer M, Cheng S, Jain M, Ngoy S, Theodoropoulos C, Trujillo A . Echocardiographic speckle-tracking based strain imaging for rapid cardiovascular phenotyping in mice. Circ Res. 2011; 108(8):908-16. PMC: 3376717. DOI: 10.1161/CIRCRESAHA.110.239574. View

Perea-Gil I, Prat-Vidal C, Bayes-Genis A . In vivo experience with natural scaffolds for myocardial infarction: the times they are a-changin'. Stem Cell Res Ther. 2015; 6:248. PMC: 4681026. DOI: 10.1186/s13287-015-0237-4. View

Endoh M . Force-frequency relationship in intact mammalian ventricular myocardium: physiological and pathophysiological relevance. Eur J Pharmacol. 2004; 500(1-3):73-86. DOI: 10.1016/j.ejphar.2004.07.013. View

Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N, Yamanaka S . Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One. 2011; 6(8):e23657. PMC: 3158088. DOI: 10.1371/journal.pone.0023657. View

Tulloch N, Muskheli V, Razumova M, Korte F, Regnier M, Hauch K . Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res. 2011; 109(1):47-59. PMC: 3140796. DOI: 10.1161/CIRCRESAHA.110.237206. View

Chen W, Baily J, Corselli M, Diaz M, Sun B, Xiang G . Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells. 2014; 33(2):557-73. PMC: 4762368. DOI: 10.1002/stem.1868. View

Menasche P, Vanneaux V, Hagege A, Bel A, Cholley B, Cacciapuoti I . Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J. 2015; 36(30):2011-7. DOI: 10.1093/eurheartj/ehv189. View

10.

Bian W, Liau B, Badie N, Bursac N . Mesoscopic hydrogel molding to control the 3D geometry of bioartificial muscle tissues. Nat Protoc. 2009; 4(10):1522-34. PMC: 2924624. DOI: 10.1038/nprot.2009.155. View

11.

Yamashita J . ES and iPS cell research for cardiovascular regeneration. Exp Cell Res. 2010; 316(16):2555-9. DOI: 10.1016/j.yexcr.2010.04.004. View

12.

Weinberger F, Breckwoldt K, Pecha S, Kelly A, Geertz B, Starbatty J . Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Sci Transl Med. 2016; 8(363):363ra148. DOI: 10.1126/scitranslmed.aaf8781. View

13.

Riegler J, Tiburcy M, Ebert A, Tzatzalos E, Raaz U, Abilez O . Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. Circ Res. 2015; 117(8):720-30. PMC: 4679370. DOI: 10.1161/CIRCRESAHA.115.306985. View

14.

Masumoto H, Nakane T, Tinney J, Yuan F, Ye F, Kowalski W . The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages. Sci Rep. 2016; 6:29933. PMC: 4951692. DOI: 10.1038/srep29933. View

15.

Fujimoto K, Clause K, Liu L, Tinney J, Verma S, Wagner W . Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function. Tissue Eng Part A. 2010; 17(5-6):585-96. PMC: 3043979. DOI: 10.1089/ten.TEA.2010.0259. View

16.

Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S . Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep. 2014; 4:6716. PMC: 4205838. DOI: 10.1038/srep06716. View

17.

Lalit P, Hei D, Raval A, Kamp T . Induced pluripotent stem cells for post-myocardial infarction repair: remarkable opportunities and challenges. Circ Res. 2014; 114(8):1328-45. PMC: 4016859. DOI: 10.1161/CIRCRESAHA.114.300556. View

18.

Ozerdem U, Grako K, Monosov E, Stallcup W . NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn. 2001; 222(2):218-27. DOI: 10.1002/dvdy.1200. View

19.

Chong J, Yang X, Don C, Minami E, Liu Y, Weyers J . Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014; 510(7504):273-7. PMC: 4154594. DOI: 10.1038/nature13233. View

20.

Sun X, Altalhi W, Nunes S . Vascularization strategies of engineered tissues and their application in cardiac regeneration. Adv Drug Deliv Rev. 2015; 96:183-94. DOI: 10.1016/j.addr.2015.06.001. View